Journal on Developmental Disabilities
Le journal sur les handicaps du développement

Abstract

Neurofibromatosis type 1 (NF1) is a disorder caused by mutations in a single gene. These mutations result in neurological dysfunction including learning disabilities in children and cognitive impairment in adults. Individuals with NF1 often develop benign and sometimes malignant neoplasms of the brain and peripheral nerves. The underlying gene responsible for these defects is the NF1 gene, which is located on chromosome 17q11.2. The NF1 gene encodes a protein called neurofibromin. One known function of neurofibromin is to inhibit another gene called Ras from sending signals to other genes and proteins. Mutations of the NF1 gene disrupt neurofibromin function, impairing its ability to inhibit Ras. This lack of inhibition of Ras, which is equivalent to its aberrant activation, underlie the basis of tumour formation in NF1. Although most tumours are benign, some may acquire further mutations that lead to malignant transformation. Studies in mice are now beginning to suggest that aberrant activation of Ras by NF1 mutations also promotes inhibition of synapse function by the neurotransmitter gamma-aminobutyric acid (GABA), and impairs a process called long-term potentiation. Such events may account for the learning and cognitive deficits seen in humans. Unusual terms in the text of the paper are explained in a glossary. 

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